Camphorylsulfonic acid esters



Patented Sept. 14, 1954 CAMPHORYLSULFONIC ACID ESTER-S OF HYDROXY SUBSTITUTED NAPI-I- THALEN'ES Quentin E. Thompson, Belleville, 111., assignor to Monsanto Chemical Company, St. Louis, Mo., a corporation of Delaware No Drawing. Application November 7, 1952, Serial No. 319,409

12 Claims. 1

This invention relates to new and useful camphorylsulfonic acid esters of hydroxy substituted naphthalenes. More specifically this invention relates to camphorylsulfonic acid esters of 1 hydroxy-Z-alkoxy-4-keto4amethyl-1,4,- 4a,5,8,8a-hexahydronaphthalenes, which ketcesters may be represented by the structural formula (I? OH;

R-SO2 where R, is a camphoryl radical, and where R is a short chain alkyl radical such as methyl, ethyl, propyl, butyl, amyl, etc.

The new keto-esters of this invention are chiefly high melting solids and are useful as plasticizers of cellulose nitrate.

The trans isomers of the new keto-esters are particularly useful in the preparation of "transbicyclic ketones, i. e. compounds of the structural formula (trans Z-ketoia-methyl1,2,4a,5,8,8a-hexahydronaphthalene) which trans-bicyclic ketones are important intermediates in the total synthesis of steroids having cortisone-like activity (J. A. C. 3., vol. 74, p. 4223ff, September, 1952). For example, by reacting a trans-isomer of a keto-ester of this invention with an excess of an equimolecular amount of lithium aluminum hydride (LiAlI-Li) in an ether solvent therefor, followed by sulfuric acid hydrolysis, good yields of the corresponding trans-bicyclic ketone are obtained.

The new keto-esters upon reductive deacylation with such reducing agents as zinc dust and acetic acid yield 2-alkoxy-4-keto-4a-methy1-1,4,- 4a,5,8,8a-hexahydronaphthalenes, which compounds may be represented by the structural formula (H) CH3 2 l These alkoxy substituted naphthalenes are described and claimed in co-pending application Serial No. 325,703, filed December 12, 1952, of A. J. Speziale.

It will be obvious to those skilled in the art that the fused bicyclic nucleus of the new compounds of this invention contain three optically active carbon atoms. As a result thereof, the new compounds may exist in eight optically active isomeric forms or four racemates. All such forms of the new esters are contemplated as coming within the scope of this invention. It is to be understood that where no notation appears with the name of the ester that the name is to be interpreted in its generic sense, i. e., as representing the individual isomers in separated form as well as the racemic mixtures thereof or the total unresolved mixture of isomers. The name of the ester of itself does not merely represent the unresolved mixture of isomers.

As illustrative of the new compounds and the preparation thereof is the following.

Example I To a suitable reaction vessel containing 20.8

parts by weight (substantially 0.1 mole) of ditrans-1-hydroxy-4-keto-2-methoxy 4a methyl-1,4,4a,5,8,Ba-hexahydronaphthalene and approximately 50 parts by weight of pyridine is slowly added with agitation 23.2 parts by weight (substantially 0.1 mole) of d-camphor-lO-sulfonyl chloride. While maintaining the temperature below 50 C. the mix is agitated for about 2 hours. The mushy reaction mixture is then poured into 250 parts by weight of an ice cold 3 molar hydrochloric acid solution and the cooled mix so obtained filtered. Approximately 37.4 parts by weight of a white crystalline solid identified as dZ-trans-ld-camphor-10-sulfonyloxy)- l-keto-Z-methOXyia-methyl-1,4, ia,5,8,8a hexahydronaphthalene possessing a melting point of -140" C. is obtained. Fractional recrystallization of the diastereoisomeric mixture from benzene gives the more insoluble Z-trans-l-(d-camphor 10 sulfonyloxy) -4keto-2-methoxy 4amethyl 1,4,4a,5,8,8a hexahydronaphthalene, melting point 166-167 C. The more soluble dextro rotating diastereoisomer, namely d-trans-l- (d-camphor-l0-sulfonyloxy) -4-keto-2-methoxy- 4a-methyl-1,4,4a,5,8,8a hexahydronaphthalene is obtained by concentrating the mother liquors followed by recrystallization. This ester possesses a melting point of1'74-175 (J.v

3 Example II Employing the procedure of Example I but replacing d-camphor-lO-sulfonyl chloride with an equimolecular amount of l-camphor-lO-sulfonyl chloride substantially white crystalline dl-transl-(l camphor-lO-sulfonyloxy)-4-keto-2-methoxy 4a methyl-1,4,4a,5,8,8a-hexahydronaphthalene is obtained in an excellent yield. Fractional recrystallization of the diastereoisomeric mixture from acetone gives the more insoluble dextro rotating diastereoisomer which possesses a melting point of 16 6-167 C. By concentrating the mother liquors and recrystallizing the more soluble levo isomer is obtained. It possesse a melting point of 174-175" C.

Example I II In accordance with the procedure of Example I an excellent yield of .dZ-trans-l-(3-bromo-dcamphor-lO-sulfonyloxy)-'4-keto 2 methoxy- 4a-methyl 1,4,4a,5;8,'8a hexahydronaphthalene is obtained employing the following reactants Parts by weight dl-Trans-l-hydroxy-4keto 2 methoxy- 4a-methyl-l,4,4a,5,8,8a hexahydronaphthalene 20.8 Diastereoisomeric 3 bromo-clcamphor-10 sulfonyl chlorides 33.0 Pyridine 50.0

Example IV In accordance with the .procedure of Example I an excellent yield .of dl-trans-(dwamphor-IO- sulfonyloxy) 4 keto 2 n butoxy 4amethyl l,4,4a,5,8,8a hexahydronaphthalene is obtained employing the following reactants Parts by weight dl Trans 1 hydroxy 4 keto 2 nbutoxy 4a methyl 1,4,4a,5, 8,8a hexahydronaphthalene 25.0 d-Camphor-lO-sulfonyl chloride 23.2 Pyridine 50.0

Example V In accordance with the procedure of Example I an excellent yield of .dl-trans-l-(d-camphor- 10 sulfonyloxy) 4 keto 2 ethoxy 4amethyl 1,4,4a,5,8,8a hexahydronaphthalene is obtained employingthe following reactants Partsby weight nZl Trans 1 hydroxy 4 keto 2- ethoxy 4a methyl 1,4,4a,5,-8,8a.- hexahydronaphthalene 22.0 d-Camphor-10-sulfonyl chloride 23.2 Pyridine 50.0

Example VI In accordance with the procedure of Example I an excellent yield of white solid l-(d-camphor- 10 sulfonyloxy) 4 keto 2 methoxy 4amethyl-l,4,4a,5,8,8a-hexahydronaphthalene is obtained employing the following reactants Parts by weight 1 hydroxy 4 keto 2 methoxy 4amethyl 1,4,4a,5,3,8a hexahydronaphthalene 21.0

cl-Camphor-lO-sulfonyl chloride I 23.2 Pyridine 50.0

Example VII In accordance with the procedure of Example I an excellent yield of dl-trans-l-(d-camphor- 10 sulfonyloxy) --4 keto- 2 n -propoxy- 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene is obtained employing the following reactants Parts by weight all Trans 1 hydroxy 4 keto 2 npropoxy 4a methyl 1,4,4a,5,8;8a hexahydronaphthalene 23.6 d-Camphor-lO-sulfonyl chloride 23.2 Pyridine 50.0

Example VIII In accordance with the procedure of Example I an excellent yield of dl-cis-l-(3-bromo-d-camphor l0 sulfonyloxy) 4 keto 2 methoXy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene is obtained employing the following reactants Parts by weight dl Cis 1 hydroxy 4 keto 2 methoxy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene 20.6 Diastereoisomeric 3 bromo d camphor- 10-sulfonyl chlorides 33.0 Pyridine 50.0

In addition to the esters prepared in the preceding examples, the following examples are further illustrations of compounds coming within the scope of this invention:

1 (camphor 10 sulfonyloxy) 4 keto 2- n pentoxy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene (camphor 1r sulfonyloxy) 4 keto 2- methoxy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene 1 (3 bromo l camphor 10 sulfonyloxy) 4 keto 2 methoxy 4a methyl 1,4,4a,-

5,8,Sa-hexahydronaphthalene (3 chloro d camphor 10 sulfonyloxy) 4 keto 2 -methoxy 4a methyl 1,4,4a,

5,8,8a-hexahydronaphthalene 1 (3 bromo camphor 'n' sulfonyloxy) 4- keto 2 methoxy 4a methyl 1,4,4a,5, 8,8a-hexahydronaphthalene 1 (3 chloro camphor 1r sulfonylcxy)- 4 keto 2 methoxy 4a methyl 1,4,4a,

5,8,Sa-heXahydrQnaphthalene (camphor 3 sulfonyloxy) 4 keto 2- methoxy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene The keto-alcohol reactants employed in the preparation of the-new'keto-esters are readily prepared by partially reducing the corresponding 1,4-diketo compound, as for example by reacting a mixture comprising zinc dust, acetic acid and a 1,4-diketo compound of the structural formula 0 CH3 ll at i (2 alkoxy 1,4 diketo 4a methyl 1,4,4a,

5,8,8a-hexahydronaphthalene) where R has the same significance as aforedescribed. Such 1,4-diketo compounds are well known chemical compounds and many of them are important intermediates in the total synthesis of steroids having cortisone-like activity (J. A. C. 8., Vol. 74; p.-42231f, September, 1952).

Although the preceding examples have described certain specific embodiments of this invention both as to the nature of the novel esters and their method of preparation, it is to be understood that substantial variations obvious to those skilled in the art in the reactants and reaction conditions set forth above, e. g. while temperatures of from about 40 C. to about 60 C. are preferred, reaction temperatures of about C. to reflux temperatures may be used, and while substantially equimolar proportions of the respective sulfonyl halide and hydroxy naphthalene reactants are preferred from 0-25% molar excess sulfonyl halide reactant may be employed when desirable, etc., may be made without departing from the spirit or scope of this invention.

What is claimed is:

1. As new compounds esters of the structural formula (I? OH;

R-SO2-O where R is a camphoryl radical and where R is a short chain alkyl radical.

2. As new compounds esters of the structural formula W CH3 CHaO I RSOz-O where R is a IO-camphoryl radical.

3. The trans isomers of the esters of claim 2. 4. As new compounds esters of the structural formula CHzO l R-SO: where R is the camphoryl radical.

5. 1-(d-camphor-10-su1fony1oxy) -4 keto-2- methoxy 4a methyl 1,4,4a,5,8,8a hexahydronaphthalene.

6. dZ-Trans-l- (d-camphor -10- sulfonyloxy) -4- keto-2-methoXy-4a-methy1-1,4,4a,5,8,8a-hexahydronaphthalene.

'7. dZ-Trans-l-(Z-camphor 10 sulfonyloxy) 4 keto 2 methoxy 4a methyl 1,4,4a,5,8,8ahexahydronaphthalene.

8. Z-Trans-l-(d-camphor 10 sulfonyloxy) -4- keto 2 methoxy 4a methyl l,4,4a,5,8,8ahexahydronaphthalene.

9. d-Trans-l-(d-camphor -10- sulfony1oxy)-4- keto-Z-methoxy-la-methyl-l,4,4a,5,8,8a-hexahydronaphthalene.

10. The process of making the esters of claim 2 which comprises reacting a keto-alcohol of the formula and a camphoryl-lO-sulfonyl chloride in pyridine.

11. The process of making the esters of claim 4 which comprises reacting 1-hydr0xy-4-keto-2- methoxy -4=amethyl 1,4,4a,5,8,8a hexahydronaphthalene and camphoryl sulfonyl chloride in pyridine.

12. The process of making the ester of claim 6 which comprises reacting dZ-trans-l-hydroxy-lketo-2-methoxy-4a-methy1-1,4,4a,5,8,8a-hexahydronaphthalene and d-camphor-lO-sulfonyl chloride in pyridine.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,373,298 Dougherty et al. Apr. 10, 1945 

1. AS NEW COMPOUNDS ESTERS OF THE STRUCTURAL FORMULA 